The overall aim of this proposal is to develop vaccine candidates which will induce protective antibody response for the prevention of M. tuberculosis infections. In contrast to other vaccine strategies for tuberculosis, this strategy will rely on activating the humoral immune response. Studies from our group have shown that a murine monoclonal antibody (mAb) 9d8, which recognizes the mycobacterial polysaccharide arabinomannan, enhances survival in mice infected with M. tuberculosis. These results suggest that arabinomannan may be a biologically important target for the humoral immune system. Our experimental approach will be to identify additional protective monoclonal antibodies to arabinomannan, which will be used to isolate arabinomannan fractions rich in protective epitopes; conjugate arabinomannan to a protein carrier and demonstrate its ability to elicit a protective antibody response. The specific aims of this project are: 1) To generate and identify protective monoclonal antibodies to arabinomannan. 2) To isolate mycobacterial arabinomannan fractions and generate candidate vaccines. 3) To determine the protective efficacy of arabinomannan and arabinomannan-protein conjugate vaccine candidates against Mtb infection.